The first requirements for studying regulatory mechanisms of metastatic phenotype is development of genetically related cellular systems containing the cell lines with with low and high metastatic capacity. Starting from murine melanoma 1735 clone M2, a series of highly metastatic lines have been established using serial transplantation in the animals, serial passages of cells in culture and invasion through amnion and corion membranes. Experiments demonstrate that the group of lines named TK (direct derivative from 1735-M2), TK-R (direct derivative from TK originating from metastatic nodules in the Rib), TK-L (derivative from TK, originating from metastatic nodules in the lung), TK-Li (derivative from TK line, originating from metastatic nodules in the liver) produce 10X more metastasis in the lung after intravenous infection than the parent line does. Syngeneic or NIH-nude mice injected with TK line and derivatives develop much higher numbers of metastatic nodules in the lung. The mice do not survive for more than 14 to 17 days. Injection of 1735 cell line does not affect the survival of the same animals for more than 4 to 5 weeks. According to previous findings, highly metastatic TK cells lines produce more collagenous type IV than low metastatic lines. Doubling time is approximately the same. In vitro migration assays demonstrate higher migratory capacity of TK cells than do metastatic cells.